Brain malformations and seizures by impaired chaperonin function of TRiC

IF 44.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Science Pub Date : 2024-10-31 DOI:10.1126/science.adp8721
Florian Kraft, Piere Rodriguez-Aliaga, Weimin Yuan, Lena Franken, Kamil Zajt, Dimah Hasan, Ting-Ting Lee, Elisabetta Flex, Andreas Hentschel, A. Micheil Innes, Bixia Zheng, Dong Sun Julia Suh, Cordula Knopp, Eva Lausberg, Jeremias Krause, Xiaomeng Zhang, Pamela Trapane, Riley Carroll, Martin McClatchey, Andrew E. Fry, Lisa Wang, Sebastian Giesselmann, Hieu Hoang, Dustin Baldridge, Gary A. Silverman, Francesca Clementina Radio, Enrico Bertini, Andrea Ciolfi, Katherine A Blood, Jean-Madeleine de Sainte Agathe, Perrine Charles, Gaber Bergant, Goran Čuturilo, Borut Peterlin, Karin Diderich, Haley Streff, Laurie Robak, Renske Oegema, Ellen van Binsbergen, John Herriges, Carol J. Saunders, Andrea Maier, Stefan Wolking, Yvonne Weber, Hanns Lochmüller, Stefanie Meyer, Alberto Aleman, Kiran Polavarapu, Gael Nicolas, Alice Goldenberg, Lucie Guyant, Kathleen Pope, Katherine N. Hehmeyer, Kristin G. Monaghan, Annegret Quade, Thomas Smol, Roseline Caumes, Sarah Duerinckx, Chantal Depondt, Wim Van Paesschen, Claudine Rieubland, Claudia Poloni, Michel Guipponi, Severine Arcioni, Marije Meuwissen, Anna C. Jansen, Jessica Rosenblum, Tobias B. Haack, Miriam Bertrand, Lea Gerstner, Janine Magg, Olaf Riess, Jörg B. Schulz, Norbert Wagner, Martin Wiesmann, Joachim Weis, Thomas Eggermann, Matthias Begemann, Andreas Roos, Martin Häusler, Tim Schedl, Marco Tartaglia, Juliane Bremer, Stephen C. Pak, Judith Frydman, Miriam Elbracht, Ingo Kurth
{"title":"Brain malformations and seizures by impaired chaperonin function of TRiC","authors":"Florian Kraft,&nbsp;Piere Rodriguez-Aliaga,&nbsp;Weimin Yuan,&nbsp;Lena Franken,&nbsp;Kamil Zajt,&nbsp;Dimah Hasan,&nbsp;Ting-Ting Lee,&nbsp;Elisabetta Flex,&nbsp;Andreas Hentschel,&nbsp;A. Micheil Innes,&nbsp;Bixia Zheng,&nbsp;Dong Sun Julia Suh,&nbsp;Cordula Knopp,&nbsp;Eva Lausberg,&nbsp;Jeremias Krause,&nbsp;Xiaomeng Zhang,&nbsp;Pamela Trapane,&nbsp;Riley Carroll,&nbsp;Martin McClatchey,&nbsp;Andrew E. Fry,&nbsp;Lisa Wang,&nbsp;Sebastian Giesselmann,&nbsp;Hieu Hoang,&nbsp;Dustin Baldridge,&nbsp;Gary A. Silverman,&nbsp;Francesca Clementina Radio,&nbsp;Enrico Bertini,&nbsp;Andrea Ciolfi,&nbsp;Katherine A Blood,&nbsp;Jean-Madeleine de Sainte Agathe,&nbsp;Perrine Charles,&nbsp;Gaber Bergant,&nbsp;Goran Čuturilo,&nbsp;Borut Peterlin,&nbsp;Karin Diderich,&nbsp;Haley Streff,&nbsp;Laurie Robak,&nbsp;Renske Oegema,&nbsp;Ellen van Binsbergen,&nbsp;John Herriges,&nbsp;Carol J. Saunders,&nbsp;Andrea Maier,&nbsp;Stefan Wolking,&nbsp;Yvonne Weber,&nbsp;Hanns Lochmüller,&nbsp;Stefanie Meyer,&nbsp;Alberto Aleman,&nbsp;Kiran Polavarapu,&nbsp;Gael Nicolas,&nbsp;Alice Goldenberg,&nbsp;Lucie Guyant,&nbsp;Kathleen Pope,&nbsp;Katherine N. Hehmeyer,&nbsp;Kristin G. Monaghan,&nbsp;Annegret Quade,&nbsp;Thomas Smol,&nbsp;Roseline Caumes,&nbsp;Sarah Duerinckx,&nbsp;Chantal Depondt,&nbsp;Wim Van Paesschen,&nbsp;Claudine Rieubland,&nbsp;Claudia Poloni,&nbsp;Michel Guipponi,&nbsp;Severine Arcioni,&nbsp;Marije Meuwissen,&nbsp;Anna C. Jansen,&nbsp;Jessica Rosenblum,&nbsp;Tobias B. Haack,&nbsp;Miriam Bertrand,&nbsp;Lea Gerstner,&nbsp;Janine Magg,&nbsp;Olaf Riess,&nbsp;Jörg B. Schulz,&nbsp;Norbert Wagner,&nbsp;Martin Wiesmann,&nbsp;Joachim Weis,&nbsp;Thomas Eggermann,&nbsp;Matthias Begemann,&nbsp;Andreas Roos,&nbsp;Martin Häusler,&nbsp;Tim Schedl,&nbsp;Marco Tartaglia,&nbsp;Juliane Bremer,&nbsp;Stephen C. Pak,&nbsp;Judith Frydman,&nbsp;Miriam Elbracht,&nbsp;Ingo Kurth","doi":"10.1126/science.adp8721","DOIUrl":null,"url":null,"abstract":"<div >Malformations of the brain are common and vary in severity, from negligible to potentially fatal. Their causes have not been fully elucidated. Here, we report pathogenic variants in the core protein-folding machinery TRiC/CCT in individuals with brain malformations, intellectual disability, and seizures. The chaperonin TRiC is an obligate hetero-oligomer, and we identify variants in seven of its eight subunits, all of which impair function or assembly through different mechanisms. Transcriptome and proteome analyses of patient-derived fibroblasts demonstrate the various consequences of TRiC impairment. The results reveal an unexpected and potentially widespread role for protein folding in the development of the central nervous system and define a disease spectrum of “TRiCopathies.”</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6721","pages":""},"PeriodicalIF":44.7000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science","FirstCategoryId":"103","ListUrlMain":"https://www.science.org/doi/10.1126/science.adp8721","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

Malformations of the brain are common and vary in severity, from negligible to potentially fatal. Their causes have not been fully elucidated. Here, we report pathogenic variants in the core protein-folding machinery TRiC/CCT in individuals with brain malformations, intellectual disability, and seizures. The chaperonin TRiC is an obligate hetero-oligomer, and we identify variants in seven of its eight subunits, all of which impair function or assembly through different mechanisms. Transcriptome and proteome analyses of patient-derived fibroblasts demonstrate the various consequences of TRiC impairment. The results reveal an unexpected and potentially widespread role for protein folding in the development of the central nervous system and define a disease spectrum of “TRiCopathies.”
TRiC的伴侣蛋白功能受损导致脑畸形和癫痫发作
脑部畸形很常见,严重程度不一,有的可以忽略不计,有的则可能致命。其病因尚未完全阐明。在此,我们报告了脑畸形、智力障碍和癫痫发作患者中核心蛋白质折叠机制 TRiC/CCT 的致病变异。伴侣素 TRiC 是一种强制性异质偶联物,我们发现了其八个亚基中七个亚基的变异,所有这些变异都通过不同的机制损害了其功能或组装。对源自患者的成纤维细胞进行的转录组和蛋白质组分析表明了 TRiC 受损的各种后果。研究结果揭示了蛋白质折叠在中枢神经系统发育过程中意想不到的潜在广泛作用,并定义了 "TRiCopathies "的疾病谱。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Science
Science 综合性期刊-综合性期刊
CiteScore
61.10
自引率
0.90%
发文量
0
审稿时长
2.1 months
期刊介绍: Science is a leading outlet for scientific news, commentary, and cutting-edge research. Through its print and online incarnations, Science reaches an estimated worldwide readership of more than one million. Science’s authorship is global too, and its articles consistently rank among the world's most cited research. Science serves as a forum for discussion of important issues related to the advancement of science by publishing material on which a consensus has been reached as well as including the presentation of minority or conflicting points of view. Accordingly, all articles published in Science—including editorials, news and comment, and book reviews—are signed and reflect the individual views of the authors and not official points of view adopted by AAAS or the institutions with which the authors are affiliated. Science seeks to publish those papers that are most influential in their fields or across fields and that will significantly advance scientific understanding. Selected papers should present novel and broadly important data, syntheses, or concepts. They should merit recognition by the wider scientific community and general public provided by publication in Science, beyond that provided by specialty journals. Science welcomes submissions from all fields of science and from any source. The editors are committed to the prompt evaluation and publication of submitted papers while upholding high standards that support reproducibility of published research. Science is published weekly; selected papers are published online ahead of print.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信